Beta-4-morpholinoethyl-benzoate salt of penicillin



Patented Oct. 6, 1953 UNITED STATES PATENT OFFICE BETA-4-MORPHOLINOETHYL-BENZOATE SALT F PENICILLIN Harley W. Rhodehamel, Jr., Indianapolis, Ind., assignor to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana N 0 Drawing. Application February 13, 1952, Serial No. 271,447

2 Claims. (Cl. 260239.1)

This invention relates to a novel penicillin The mixture is cooled and stirred occasionally salt and the preparation thereof. whereupon the slightly soluble p-l-morpholino- I have discovered that B-4-morpholinoethyl ethyl benzoate salt of penicillin G precipitates. benzoate or its salts can be combined with peni- The salt is separated, and dried in vacuo. cillin or its salts by neutralization or metatheti- 5 s-e-morpholinoethyl benzoate can be prepared cal reactions to form a sparingly soluble peniby esterification of benzoic acid with ,6-4-m0rcillin salt, thereby afiording a means of precippholinoethanol. The salts of p-4-morpholinoitating penicillin from solution, and of purifyethyl benzoate are prepared by the usual mething penicillin. Moreover, the novel penicillin salt ods, as by the interreaction of equivalent amounts can be utilized therapeutically. A prolonged of the base and a selected acid in inert solvent penicillin blood level can be secured upon adsolution, followed by removal of the solvent. ministering the salt parenterally by methods Iclaim: known to the medical art. 1. The 18-4-morpholinoethyl benzoate salt of The following examples illustrate the prepapenicillin represented by the following formula ration of the novel salt of this invention: in which Prepresents penicillin:

Example 1 E" To a solution of 3 g. of penicillin (e. g. a commercial mixture of the several penicillins) dis- P a-O solved in 35 ml. of amyl acetate are added 3 g. 20 of fll-morpholinoethyl benzoate dissolved in 50 ml. of amyl acetate. The mixture is cooled and stirred occasionally whereupon the p-4-morpholinoethyl benzoate salt of penicillin precipitates. The salt is isolated as by decantation or filtration, 5

2. The fll-morpholinoethyl benzoate salt of penicillin G.

HARLEY W. RHODEHAMEL, JR.

and dried in vacuo References Cited in the file of this patent The salt is represented by the following for- UNITED STATES PATENTS mula in which P represents penicillin: Number Name Date 5 2,515,898 Rhodehamel July 18, 1950 FOREIGN PATENTS P 0112-011 Number Country Date 659,775 Great Britain Oct. 24, 1951 Example 2 OTHER REFERENCES To an aqueous solution of 0.3 g. of the potas- Ballaro: Ciencia e Investigacion, vol. 4, Nosium salt of penicillin G in 1.8 ml. of water is vember1948,pp.481,482. added a solution of 0.3 g. of p-4-morpholino- Rhodehamel: J. Am. Chem. 800., vol. 73, De-

ethyl benzoate hydrochloride in 5 ml. of water. cember 1951, p. 5902. 

1. THE B-4-MORPHOLINOETHYL BENZOATE SALT OF PENICILLIN REPRESENTED BY THE FOLLOWING FORMULA IN WHICH P REPRESENTS PENICILLIN: 